Field
This invention relates in general to the measurement of liquid-sample volumes and, more specifically, to the use of low-coherence optical interferometry toward that end.
Description of Related Art
In a typical laboratory setting, several small reaction vessels are arranged in a rectangular microplate. These microplates have standardized, common outer dimensions and contain a varying number of vessels, which are referred to as wells. The most common cases are 96, 384, and 1536 wells. The volume of the individual well decreases as the well density of the plate increases. Standardized microplates allow for the use of automated liquid delivery and analysis devices. In many real-world examples, an automatic liquid delivery device is programmed to add specific volumes of various liquids to each of the reaction vessels or wells in a microplate. Subsequently, an automatic analysis device interrogates each of the wells and measures one or several physical or chemical properties. One common example is to read the optical absorbance or emitted fluorescence from each well with a plate reader, but many other measurements are carried out in practice.
In this type of experiment, researchers often derive their knowledge of the volume of liquid added to each well from the instructions sent to the liquid delivery device. Specifically, they rely on the liquid delivery device to add a volume to the well that matches the desired volume as closely as possible. It is, therefore, useful to provide a device whose use enables the independent verification of the performance of the liquid delivery device. In particular, it is useful to provide a device whose use enables the user to independently verify by how much the actually dispensed volume differs from the desired dispense volume. This property is called the accuracy of the liquid delivery device. Similarly, it is important that for the same desired dispense volume, the actual dispense volume exhibit little variation. This property is called the precision of the liquid delivery device.
In practice, automated liquid delivery devices provide for a set of instrument parameters that can be adjusted by the user to ensure that desired dispense volume and actual dispense volume match. Configuring a liquid delivery device for a given experiment by adjusting this set of parameters to ensure accuracy and precision of the liquid delivery device for the specific liquids used in that experiment is one of the most important tasks in reducing the contribution of the liquid delivery device to experimental errors. Typically, a specific set of values has to be chosen for these instrument parameters for each kind of liquid that is being dispensed. Hence, a common industry term for this set of parameters is “liquid class”. Often, instrument parameters also have to be adjusted for dispensing different volume ranges.
The optimal values for this set of instrument parameters may vary from liquid to liquid. This is a result of the physical and chemical properties of the liquid and the configuration of those parts of the liquid delivery instrument the liquid is in contact with. Examples for important aspects of the configuration are pipet and tubing wall materials and dimensions as well as dispense speeds. Among the properties of the liquid that come into play are its surface tension, which describes the interaction with the gas above the liquid, and the interfacial tensions, which describe the interaction with solid materials the liquid comes in contact with. The viscosity of the liquid and the temperature also play an important role.
Currently, researchers use various approaches to verify the performance of liquid delivery devices.